This invention relates to the purification of glycolide. More particularly, the invention is concerned with the purification of commercially available glycolide to a purity which maks it suitable for the production of suture-grade polyglycolid acid.
It is known that polyglycolic acid (PGA), also known as polyhydroxyacetic acid, is a suitable material for synthetic absorbable sutures to replace the traditional collagen ("catgut") sutures. Among the advantages of using synthetic polymers over the previously used collagenous material are predictable formability and consistency in characteristics, such as absorbability and stiffness. Of the various synthetic materials which have been suggested for the production of sutures, polyglycolic acid is particularly suitable because of a number of desirable characteristics including handleability, strength, non-toxicity, sterility and absorbability. Regarding absorbability, it is desirable that a suture material retains its strength long enough for the wound to heal before substantial absorption occurs and that an appropriate grade of polyglycolic acid be chosen so as to give the desired rate of absorption. It has been found that polyglycolic acid having an inherent viscosity, .eta. inh, of 1.1 to 1.6, preferably about 1.3, has the required characteristics for sutures.
Numerous references relating to the production and use of sutures made from polyglycolic acid have been published in the art. Exemplary of such references is U.S. Pat. No. 3,297,033, to Schmitt et al, which discloses the production of a synthetic absorbable surgical suture from a polyhydroxyacetic ester. The Schmitt et al Patent also discloses that a preferred route for the preparation of the said polyhydroxyacetic ester involves the polymerization of glycolide: ##STR1## the cyclic dimeric condensation product formed by dehydrating hydroxyacetic acid.
According to U.S. Pat. No. 3,297,033 the polymerization of glycolide occurs by heating with or without a catalyst, or may be induced by radiation such as x-rays, gamma rays or electron beams. The catalyst disclosed in this Patent is antimony trifluoride.
Another process for polymerizing a glycolide is disclosed in U.S. Pat. No. 3,442,871, also to Schmitt et al. This patent discloses the polymerization of a substantially pure glycolide, which may be .alpha.-glycolide alone, or .beta.-glycolide alone or a mixture of the .alpha.- and .beta.-glycolide isomers, which comprises heating a mixture containing the glycolide and from about 0.05 to 1.5 mole percent of an alcohol free of non-benzenoid unsaturation, e.g. lauryl alcohol, in the presence of a minor proportion of SnCl.sub.2.2H.sub.2 O as catalyst. U.S. Pat. No. 3,442,871 further emphasizes the requirement that the glycolide be "substantially pure" to provide, upon polymerization, polyglycolic acid of a suitable standard for use in sutures (herein referred to as "suture-grade" polyglycolic acid).
The preparation of glycolide in an appropriate "pure" form for polymerization to suture grade polyglycolic acid also has been the subject of intensive research in the art; and, here again, there is an extensive number of patent references relating to the production of "pure" glycolide. Illustrations of such references are U.S. Pat. Nos. 3,435,008, to Schmitt et al; 3,457,280, to Schmitt et al; and 3,763,190, to Ross et al.
It is clear from the above references that the purification of glycolide is of prime importance if the polyglycolic acid prepared by the polymerization thereof is to be suitable for the production of sutures. Paradoxically, if the glycolide is too pure the polyglycolic acid resulting from the polymerization thereof is unsuitable for sutures because of difficulty in extrusion. The glycolide of satisfactory purity is that which will provide polyglycolic acid having an inherent viscosity of 1.1 to 1.6 and suture-grade polyglycolic acid is defined herein as polyglycolic acid having said inherent viscosity.
Commercially available glycolide is not sufficiently pure to provide suture grade polyglycolic acid upon polymerization. Typical contaminants are free acid (glycolic acid) and free water, and polyglycolic acid produced by the polymerization of said glycolide typically has an inherent viscosity of about 0.8.
Surprisingly, it has now been found that said commercially available glycolide can be purified in a manner which results in losses of no more than 1 to 10% as compared with about 25 to 50% in the prior art, and consequently is much less costly than conventional distillation methods and more simple than other complex methods disclosed in the prior art; these benefits are obtained by treatment with alumina under carefully controlled conditions.